DNA damage response protein ASCIZ links base excision repair with immunoglobulin gene conversion
- 作者：Hayato Oka ; Wataru Sakai ; Eiichiro Sonoda ; Jun Nakamura ; Kenjiro Asagoshi ; Samuel H. Wilson ; Masahiko Kobayashi ; Kenichi Yamamoto ; Jö ; rg Heierhorst ; Shunichi Takeda ; Yoshihito Taniguchi
- 关键词：ASCIZ ; ATMIN ; DT40 ; Base excision repair ; Immunoglobulin gene conversion ; DNA polymerase β ; Genetics
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2008
- 期刊代码：159_0006291x
- 类别：bio
- 出版时间：27 June 2008
- 卷：371
- 期：2
- 页码：225-229
- 文件大小：324 K
摘要
ASCIZ (ATMIN) was recently identified as a novel DNA damage response protein. Here we report that ASCIZ-deficient chicken DT40 B lymphocyte lines displayed markedly increased Ig gene conversion rates, whereas overexpression of human ASCIZ reduced Ig gene conversion below wild-type levels. However, neither the efficiency of double-strand break repair nor hypermutation was affected by ASCIZ levels, indicating that ASCIZ does not directly control homologous recombination or formation of abasic sites. Loss of ASCIZ led to mild sensitivity to the base damaging agent methylmethane sulfonate (MMS), yet remarkably, suppressed the dramatic MMS hypersensitivity of polβ-deficient cells. These data suggest that ASCIZ may affect the choice between competing base repair pathways in a manner that reduces the amount of substrates available for Ig gene conversion.